LAVAL, Quebec, April 11 /CNW-PRN/ - BioChem Pharma Inc. announces that an
interim review of a long-term follow-up study involving 58 Chinese patients with
chronic hepatitis B shows that nearly half (47%; 27/58) achieved hepatitis e
antigen seroconversion after four years of treatment with Epivir-HBV(R) (lamivudine).
Seroconversion, a marker of loss of viral replication, is defined in this study
as the loss of hepatitis B e antigen and gain of antibody to e antigen. In
previous annual interim

evaluations of this study population, 29% (17/58) of the patients hadseroconverted
after two years of therapy, 40% (23/58) after three years and,now,
47% after four years of treatment with Epivir-HBV.The
data, presented today at the 10th International Symposium on ViralHepatitis
and Liver Disease, also showed that in a subset of 26 patients whoentered
the study with elevated serum alanine aminotransferase (ALT) levelsmore
than two times above the normal limit, the seroconversion rate was 73%after
four years of therapy. These data suggest that elevated pre-treatmentserum
ALT, a marker of liver inflammation, is associated with increased ratesof
seroconversion.

The results of this study are important for a variety of reasons, inparticular
the trend of incremental, steady increase in the number ofpatients
who no longer have clinical evidence of chronic hepatitis B afterextended
treatment with Epivir-HBV, and the fact that the drug appears to begenerally
well tolerated for this treatment period,'' said Dr. Ting-TsungChang,
Professor in the Department of Internal Medicine, at the NationalCheng
Kung University Hospital (Tainan, Taiwan). ``Seroconversion may predictsustained
suppression of hepatitis B virus and improved clinical prognosis.''

The study reported today is a five-year uncontrolled clinical trial involving58 adult Chinese patients with compensated chronic
hepatitis B. Studyparticipants received 100 mg
per day of Epivir-HBV. Of the original 58patients
in the study, 44 were still on treatment through four years. Fivepatients
had stopped treatment after three years, and nine additionalpatients
withdrew before the end of year 4.Hepatitis B
is an infectious disease that ranges from mild acute infectionwith
no signs or symptoms to a more serious chronic liver disease, which canlead
to severe liver scarring (cirrhosis), liver failure or liver cancer.Worldwide,
approximately one million people die annually from hepatitisB-associated
liver disease.The most important goal of
therapy for chronic hepatitis B is reducing theprogressive
liver inflammation that occurs when the immune system attackshepatitis
B-infected liver cells. Epivir-HBV acts directly to inhibit viralreplication,
leading to reduced inflammatory response to the hepatitis Bvirus
in the liver.

It was also noted in the study that 39 of 58 (67%) patients developed YMDDvariant hepatitis B virus at some point during
treatment. YMDD variants havebeen associated
with a diminished treatment response to lamivudine. However,13
of these 39 patients (33%) achieved HBeAg seroconversion despite having avariant strain of hepatitis B. In six of these
patients, seroconversionoccurred after
detection of the YMDD variants. Also, 23 of the 39 patientswho
were determined to have the YMDD variant virus had normal ALT levels attheir
last clinic visit. The long-term clinical significance of YMDD varianthepatitis
B is unknown.

The data in this study suggest that the presence of the YMDD variant strainof hepatitis B may not preclude patients from
experiencing a clinical benefitfrom treatment
with Epivir-HBV and, in some cases, from experiencingseroconversion,''
said C-L Lai, MD, Co-Chief, Division of Gastroenterologyand
Hepatology at Queen Mary Hospital, Hong Kong.Epivir-HBV
is an oral medication, dosed with one tablet daily (100 mg), thatis
indicated for the treatment of adults with compensated chronic hepatitis Bassociated with evidence of hepatitis B viral
replication and active liverinflammation.

In the 58-patient trial from which the newly presented data are drawn, onepatient experienced transient hepatic decompensation
coincident withdetection of YMDD variant, and
remained on therapy.More generally, in
clinical trials supporting the approval of Epivir-HBV,Epivir-HBV
was generally well tolerated among chronic hepatitis B patients.In
three placebo-controlled clinical trials, the most common adverse eventsobserved
in patients treated with Epivir- HBV (vs. placebo) were ear, noseand
throat infections, 25% (21%); malaise and fatigue, 24% (28%); andheadache,
21% (21%).The optimum duration of treatment,
the durability of HBeAg seroconversionsoccurring
during treatment, and the relationship of initial treatmentresponse
to outcomes such as hepatocellular carcinoma and decompensatedcirrhosis
are not known.

Lactic acidosis and severe hepatomegaly with steatosis, including fatalcases, have been reported with the use of nucleoside
analogues alone or incombination, including
lamivudine and other antiretrovirals.Human
immunodeficiency virus (HIV) counseling and testing should be offeredto
all patients before beginning Epivir-HBV and periodically during treatmentas Epivir-HBV Tablets and Oral Solution contain a
lower dose of the sameactive ingredient (lamivudine)
as Epivir(R) Tablets and Oral Solution used totreat
HIV infection. If treatment with Epivir-HBV is prescribed for chronichepatitis
B for a patient with unrecognized or untreated HIV infection, rapidemergence
of HIV resistance is likely because of subtherapeutic dose andinappropriate
monotherapy.Lamivudine for hepatitis B
is already available in many countries includingChina,
South Korea, the US, Canada, UK, Germany and France. In most marketsthe
trade name Zeffix is used; in the US it is known as Epivir-HBV; in Canadaas Heptovir and in China as Heptodin.